Defective Pollen Wall 2 (DPW2) Encodes an Acyl Transferase Required for Rice Pollen Development.

Aliphatic and aromatic lipids are both essential structural components of the plant cuticle, an important interface between the plant and environment. Although cross links between aromatic and aliphatic or other moieties are known to be associated with the formation of leaf cutin and root and seed suberin, the contribution of aromatic lipids to the biosynthesis of anther cuticles and pollen walls remains elusive. In this study, we characterized the rice (Oryza sativa) male sterile mutant, defective pollen wall 2 (dpw2), which showed an abnormal anther cuticle, a defective pollen wall, and complete male sterility. Compared with the wild type, dpw2 anthers have increased amounts of cutin and waxes and decreased levels of lipidic and phenolic compounds. DPW2 encodes a cytoplasmically localized BAHD acyltransferase. In vitro assays demonstrated that recombinant DPW2 specifically transfers hydroxycinnamic acid moieties, using ω-hydroxy fatty acids as acyl acceptors and hydroxycinnamoyl-CoAs as acyl donors. Thus, The cytoplasmic hydroxycinnamoyl-CoA:ω-hydroxy fatty acid transferase DPW2 plays a fundamental role in male reproduction via the biosynthesis of key components of the anther cuticle and pollen wall.

Regulatory Role of a Receptor-Like Kinase in Specifying Anther Cell Identity.

In flowering plants, sequential formation of anther cell types is a highly ordered process that is essential for successful meiosis and sexual reproduction. Differentiation of meristematic cells and cell-cell communication are proposed to coordinate anther development. Among the proposed mechanisms of cell fate specification are cell surface-localized Leu-rich repeat receptor-like kinases (LRR-RLKs) and their putative ligands. Here, we present the genetic and biochemical evidence that a rice (Oryza sativa) LRR-RLK, MSP1 (MULTIPLE SPOROCYTE1), interacts with its ligand OsTDL1A (TPD1-like 1A), specifying the cell identity of anther wall layers and microsporocytes. An in vitro assay indicates that the 21-amino acid peptide of OsTDL1A has a physical interaction with the LRR domain of MSP1. The ostdl1a msp1 double mutant showed the defect in lacking middle layers and tapetal cells and having an increased number of microsporocytes similar to the ostdl1a or msp1 single mutant, indicating the same pathway of OsTDL1A-MSP1 in regulating anther development. Genome-wide expression profiles showed the altered expression of genes encoding transcription factors, particularly basic helix-loop-helix and basic leucine zipper domain transcription factors in ostdl1a and msp1 Among these reduced expressed genes, one putatively encodes a TGA (TGACGTCA cis-element-binding protein) factor OsTGA10, and another one encodes a plant-specific CC-type glutaredoxin OsGrx_I1. OsTGA10 was shown to interact with OsGrx_I1, suggesting that OsTDL1A-MSP1 signaling specifies anther cell fate directly or indirectly affecting redox status. Collectively, these data point to a central role of the OsTDL1A-MSP1 signaling pathway in specifying somatic cell identity and suppressing overproliferation of archesporial cells in rice.

Effect of different noninvasive ventilation interfaces on the prevention of facial pressure injury: A network meta-analysis.

OBJECTIVE: To assess the effect of different noninvasive ventilation interfaces on preventing the facial pressure injury. METHODS: This network meta-analysis was conducted following the PRISMA reporting guidelines. Seven electronic databases were systematically searched for randomised controlled trials about the comparative effectiveness of different interfaces in preventing facial pressure injury with noninvasive ventilation in adults and newborns from inception to June 2023. The acronym of PICOS was used and the keywords as well as inclusion/exclusion criteria were determined. Study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias assessment tool was used to assess the methodological quality. RESULTS: A total of 78 randomised controlled trials involving 7,291 patients were included. The results of network meta-analysis showed that the effectiveness of the eight noninvasive ventilation interfaces on the prevention of facial pressure injury was in the order of: nasal cannula > full-face mask > rotation of nasal mask with nasal prongs > helmet > nasal mask > oronasal mask > nasal prongs > face mask. The use of full-face mask in adults and nasal cannula in newborns had the best effect on preventing the incidence of facial pressure injury. CONCLUSIONS: The use of full-face mask in adults and nasal cannula in newborns had the most clinical advantage in preventing the incidence of facial pressure injury and were worthy promoting in clinical practice. IMPLICATIONS FOR CLINICAL PRACTICE: This study provides a certain theoretical basis for the selection of appropriate interface for patients with noninvasive ventilation. Clinical practitioners should choose the appropriate interfaces based on the patient's specific condition to reduce the incidence of facial pressure injury, enhance patient comfort, and improve the effectiveness of respiratory therapy.

[Application of abdominal venous Doppler flow pattern in volume management].

Accurate assessment of hemodynamic status is crucial for volume management. Venous congestion caused by volume overload can cause organ damage and poor prognosis. Traditional critical ultrasound, including inferior vena cava ultrasound, echocardiography, and lung ultrasound, is widely used in volume management. However, it is unable to evaluate the organ blood flow. The blood flow pattern of abdominal vein changes dynamically with venous congestion, which is an index for evaluating the blood flow of hepatic vein, portal vein and internal renal vein by Doppler ultrasound. This article reviews the acquisition and grading standards of abdominal venous blood flow patterns, their application and limitations in volume management, with a view to providing help for early clinical identification of terminal organ congestion, implementation of fluid negative balance intervention and individualized volume management.

HS-10352 in hormone receptor-positive, HER2-negative advanced breast cancer: A phase 1 dose-escalation trial.

BACKGROUND: Approximately 40% of patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) exhibit PIK3CA mutations. AIMS: This study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of HS-10352, a selective PI3Kα inhibitor, in this patient population. MATERIALS AND METHODS: Conducted as a phase 1 dose-escalation trial, HS-10352 was administered orally once-daily (QD) at dose levels of 2, 4, 6, and 8 mg. The primary endpoints were dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). This study is registered at ClinicalTrials.gov (NCT04631835). RESULTS: Between August 2020 and March 2022, a total of 18 female patients were enrolled. DLT, manifested as hyperglycemia, occurred in two patients in the 8 mg QD group, establishing an MTD of 6 mg QD. The most common treatment-related adverse events were hyperglycemia (88.9%) and weight loss (61.3%). In the 6 mg QD group, four patients (66.7%) had a partial response (PR), and one (16.7%) had stable disease (SD). Among the four patients with PIK3CA mutated tumors in this dosage group, three (75.0%) had PR and one (25.0%) had SD. The median progression-free survival was not reached (95% confidence interval, 11.1-NA). DISCUSSION AND CONCLUSION: HS-10352 at 6 mg QD was well-tolerated in patients with HR-positive, HER2-negative ABC, and showed preliminary antitumor activity in patients with PIK3CA mutated tumors. These findings support the further clinical development of HS-10352.

Effect of Levothyroxine Sodium Tablets on Pregnancy Outcome and Offspring Development Quotient of SCH during Pregnancy.

Objective: To investigate the effect of levothyroxine sodium tablets (L-T4) on pregnancy outcome and offspring development quotient in patients with subclinical hypothyroidism (SCH) during pregnancy. Material and Methods. Pregnant women with gestational age less than 12 weeks who underwent the first prenatal examination in our hospital from January 2019 to December 2019 were prospectively selected as subjects. According to the level of thyroid hormone in pregnant women, they were divided into the treatment group (n = 63) and received L-T4 treatment, untreated group (n = 64), and control group (n = 54). Three groups of pregnancy outcomes, children's physical development, and the development of offspring were compared at when one full year of life. Results: After treatment, the contrast difference of the three groups about abortion and gestational diabetes mellitus (GDM) was statistically significant (P < 0.05). The abortion rate and gestational diabetes mellitus (GDM) in the untreated group were higher than those in the control group (P < 0.05). The contrast difference of the treatment group and control group about abortion and gestational diabetes mellitus (GDM) is not statistically significant (P > 0.05); The contrast difference of the three groups about a filial generation at birth and one-year-old body length is not statistically significant (P > 0.05). The contrast difference between the three groups of individual children who are one-year old having the individual action energy, material ability, speech ability, and human ability is statistically significant (P < 0.05). One-year-old developmental quotient (DQ) of the treatment group and control group was higher than that of the untreated group (P < 0.05); the Pearson correlation analysis showed that the treatment group TSH levels have no correlation between the offspring developmental quotient (DQ) level of one-year-old children (P > 0.05). Conclusion: Levothyroxine sodium tablets (L-T4) can not only improve the pregnancy outcome of patients with SCH during pregnancy but also play a positive role in improving the neurointellectual development of their offspring.

Intrarenal Doppler approaches in hemodynamics: A major application in critical care.

The treatment of severe cases usually requires multimodality hemodynamic monitoring approaches, particularly for tissue and organ perfusion tracking. Currently, only a few studies have investigated renal perfusion status at the bedside. Ultrasound has become increasingly utilized to guide the hemodynamic management of severe patients. Similarly, intrarenal Doppler (IRD) is widely used to assess renal perfusion from both the intrarenal artery and vein perspectives. The renal resistive index (RRI), which reflects the renal arterial blood flow profile, is often applied to predict the reversibility of renal dysfunction and to titrate hemodynamic support. Intrarenal venous flow (IRVF) patterns and the renal venous stasis index (RVSI), which reflects the intrarenal vein blood flow profile, are now being used to assess intravenous congestion. They may also be useful in predicting the risk of acute kidney injury and avoiding fluid overload. IRD can provide diverse and supplemental information on renal perfusion and may help to establish the early diagnosis in severe patients. This review focused on the specific operational methods, influencing factors, and applications of IRD in hemodynamics.

Prediction Models for Conversion From Mild Cognitive Impairment to Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Background and Purpose: Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no cure, and available treatments are only able to postpone the progression of the disease. Mild cognitive impairment (MCI) is considered to be a transitional stage preceding AD. Therefore, prediction models for conversion from MCI to AD are desperately required. These will allow early treatment of patients with MCI before they develop AD. This study performed a systematic review and meta-analysis to summarize the reported risk prediction models and identify the most prevalent factors for conversion from MCI to AD. Methods: We systematically reviewed the studies from the databases of PubMed, CINAHL Plus, Web of Science, Embase, and Cochrane Library, which were searched through September 2021. Two reviewers independently identified eligible articles and extracted the data. We used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS) checklist for the risk of bias assessment. Results: In total, 18 articles describing the prediction models for conversion from MCI to AD were identified. The dementia conversion rate of elderly patients with MCI ranged from 14.49 to 87%. Models in 12 studies were developed using the data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). C-index/area under the receiver operating characteristic curve (AUC) of development models were 0.67-0.98, and the validation models were 0.62-0.96. MRI, apolipoprotein E genotype 4 (APOE4), older age, Mini-Mental State Examination (MMSE) score, and Alzheimer's Disease Assessment Scale cognitive (ADAS-cog) score were the most common and strongest predictors included in the models. Conclusion: In this systematic review, many prediction models have been developed and have good predictive performance, but the lack of external validation of models limited the extensive application in the general population. In clinical practice, it is recommended that medical professionals adopt a comprehensive forecasting method rather than a single predictive factor to screen patients with a high risk of MCI. Future research should pay attention to the improvement, calibration, and validation of existing models while considering new variables, new methods, and differences in risk profiles across populations.

Efficacy of Chinese herbal prescriptions containing Ejiao or Velvet antler for management of uterine fibroids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the efficacy and safety of the controversial Chinese herbal prescriptions containing Ejiao or Velvet antler (VA) in the treatment of uterine fibroids. METHODS: We searched 4 famous Chinese databases, the Chinese Clinical Trial Registry, PubMed, Cochrane Central, Google Scholar, Embase, and J-STAGE up to July 2019. We included all eligible randomized controlled trials (RCTs) which compared Chinese herbal prescriptions containing Ejiao or VA (E/VA) with placebo, pharmaceutical intervention, surgery, or other traditional Chinese medicines (TCMs) for uterine fibroids and assessed the risk of bias according to the Cochrane Collaboration's tool. The software Review Manager (RevMan) 5.1 was used for data analysis. RESULTS: A total of 9 RCTs involving 844 patients were identified. Meta-analyses demonstrated that TCM (E/VA) plus mifepristone reduced the volume of uterine fibroids to a greater degree than mifepristone alone [standardized mean difference (SMD): 0.59, 95% CI: 0.33 to 0.85, P<0.00001, I2=50%]; TCM (E/VA) did not enlarge the volume of fibroids when menopausal hormone therapy (MHT) significantly increased the volume (SMD: 1.06, 95% CI: 0.73 to 1.38, P<0.00001, I2=0. The uterine volume change difference was larger via combination therapy of TCM (E/VA) and mifepristone than that of mifepristone (SMD: 0.29, 95% CI: 0.09 to 0.49, P=0.005, I2=0%). The TCM (E/VA) group of had an advantage over the control group in the improvement of fibroid-related symptoms [relative risk (RR): 1.24, 95% CI: 1.15 to 1.35, P<0.00001, I2=0%]. It was found that TCM (E/VA) plus mifepristone could lower estradiol (E2) levels to a greater degree than mifepristone alone (SMD: 1.63, 95% CI: 0.42 to 2.83, P=0.008, I2=97%), as well as progesterone (P) level (SMD: 0.79, 95% CI: 0.55 to 1.04, P<0.00001, I2=43%) in non-menopausal women. A total of 5 studies reported adverse events (AEs), the TCM (E/VA) group was potentially safer than the control group, with lower incidence of AEs (RR: 0.24, 95% CI: 0.15 to 0.40, P<0.00001, I2=25.8%). DISCUSSION: TCM prescriptions containing E/VA seemed superior to the control group in shrinking the volume of uterine fibroids and uterus, improving related symptoms, and reducing non-menopausal women's E2 and P levels, with lower incidence of AEs.

Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration.

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

Combined effect of hydrotherapy and transcranial direct-current stimulation on children with cerebral palsy: A protocol for a randomized controlled trial.

BACKGROUND: Cerebral palsy (CP) is a neurodevelopmental disorder caused by a brain injury resulting in poor coordination and motor control deficits, which is one of the most common physical disabilities in children. CP brings a heavy burden on families and society and becomes a significant public health issue. In recent years, hydrotherapy, and transcranial direct current stimulation (tDCS) as a physical therapy for CP is developing rapidly. When hydrotherapy and tDCS are used to treat separately, it has positive therapeutic effect in children with CP. The development of new therapies in combination with physical rehabilitation approaches is critical to optimize functional outcomes. tDCS has attracted interest in this context, because of significant functional improvements have been demonstrated in individuals with brain injuries after a short period of cerebral stimulation. Since the onset of this work, tDCS has been used in combination with constraint-induced therapy, virtual reality therapy to potentiate the treatment effect. Up to now, there are no studies on the effect of a combined application of hydrotherapy and tDCS in children with CP. We will conduct a 2-arm parallel clinical trial to investigate the effect of a combined application of tDCS and hydrotherapy. METHODS AND ANALYSIS: This study is an outcome assessor and data analyst-blinded, randomized, controlled superiority trial during the period from October 2021 to December 2023. CP patients meeting the inclusion criteria will be allocated in a 1:1 ratio into the treatment group (hydrotherapy plus tDCS), or the control group (treatment as usual). All participants will receive 30 sessions of treatment over 10 weeks. The primary outcomes will be the difference in the Gross Motor Function Assessment and Pediatric Balance Scale during rest and activity. The secondary outcomes will be the difference in adverse effects between the control and treatment groups. CONCLUSIONS: This study aims to estimate the efficacy of a combined application of tDCS and hydrotherapy in patients with CP. TRIAL REGISTRATION: This study protocol was registered in Chinese ClinicalTrials.gov, ID: ChiCTR2100047946.

Rab5a suppresses autophagy to promote drug resistance in cancer cells.

Cancers are huge problems that need to be investigated thoroughly. Rab5a plays an important part in the regulation of intracellular membrane trafficking. However, its role in cancer and autophagy has not been fully determined. In this study, we analyzed the correlation between Rab5a expression and patients' prognosis and then explored the effect of Rab5a knockdown on different cell lines using western blotting and fluorescence. Our results showed that up-regulated Rab5a positively correlated with the prognosis of gastric cancer patients. After knocking down Rab5a, mTOR activity was inhibited and autophagy flux increased. We also found that in our cisplatin-resistant cells, knockdown of Rab5a activated autophagy via mTOR pathway and could reverse drug resistance while overexpression of Rab5a in drug sensitive cells increased drug tolerance. In conclusion, our study demonstrates that Rab5a can suppress autophagy through mTOR and promote drug resistance in gastric cancer cells.

Enolase 1 stimulates glycolysis to promote chemoresistance in gastric cancer.

Chemotherapy is the major choice for the cancer treatment of early and advanced stages. However, intrinsic or acquired drug resistance significantly restricts the clinical efficacy of chemotherapy. It is critical to develop novel approaches to detect and overcome drug resistance. In this study, we demonstrated that accelerated glycolysis played a pivotal role in both intrinsic and acquired cisplatin-resistance of gastric cancer cells. The metabolic reprogramming of cisplatin-resistant cells was characterized by increased glycolysis dependence. Inhibition of glycolysis with glucose starvation or 2-Deoxy-D-glucose (2-DG) treatment significantly reversed drug resistance. By proteomic screening, we found the increased expression of the glycolytic enzyme Enolase 1 (ENO1) in cisplatin-resistant gastric cancer cells. Depletion of ENO1 by siRNA significantly reduced glycolysis and reversed drug resistance. Moreover, the increased expression of ENO1 was attributed to the down-regulation of ENO1-targeting miR-22, rather than activated gene transcriptional or prolonged protein stability. Finally, the elevated levels of ENO1 proteins were associated with the shorter overall survival of gastric cancer patients. In conclusion, ENO1 is a novel biomarker to predict drug resistance and overall prognosis in gastric cancer. Targeting ENO1 by chemical inhibitors or up-regulating miR-22 could be valuable to overcome drug resistance.

Reliability and Validity of a Chinese Version of the Stroke Action Test: A New Instrument for Assessment of Stroke Knowledge and Response.

BACKGROUND: The public's cognition of stroke and responses to stroke symptoms are important to prevent complications and decrease the mortality when stroke occurs. The aim of study was to develop and validate the Chinese version of the Stroke Action Test (C-STAT) in a Chinese population. METHODS: This study was rigorously implemented with the published guideline for the translation, adaptation and validation of instruments for the cross-cultural use in healthcare care research. A cross-sectional study was performed among 328 stroke patients and family members in the Department of Neurology in the Second Hospital of Lanzhou University, Gansu province, China in 2014. RESULTS: The Chinese version of the instrument showed favorable content equivalence with the source version. Values of Cronbach's alpha and test-retest reliability of the C-STAT were 0.88 and 0.86, respectively. Principal component analysis supported four-factor solutions of the C-STAT. Criterion-related validity showed that the C-STAT was a significant predictor of the 7-item stroke symptom scores (R = 0.77; t = 21.74, P< 0.001). CONCLUSION: The C-STAT is an intelligible and brief psychometrical tool to assess individuals' knowledge of the appropriate responses to stroke symptoms in Chinese populations. It could also be used by health care providers to assess educational programs on stroke prevention.

Regulation and role of post-translational modifications of enhancer of zeste homologue 2 in cancer development.

Post-translational modifications (PTMs) are critical molecular events which alter protein conformation after their synthesis and diversity protein properties by modulating their stability, localization, interacting partners or the activity of their substrates, consequently exerting pivotal roles in regulating the functions of many important eukaryotic proteins. It has been well acknowledged that PTMs are of great importance in a broad range of biological processes such as gene regulation, cell proliferation, differentiation and apoptosis, tissue development, diseases, tumor progression and drug resistance. As the core and contributing catalytic subunit of Polycomb repressive complex 2(PRC2), Enhancer of zeste homolog 2 (EZH2) is a master epigenetic regulator, often serving as a highly conserved histone methyltransferase (HMTase) to induce histone H3 lysine 27 trimethylation (H3K27me3) and repress gene transcription and expression. Dysregulated EZH2 expression is frequently associated with cancer development and poor prognosis in a wide variety of cancers. Considered its essential role in carcinogenesis, EZH2 is a potential candidate for cancer targeted therapy. Remarkably, mounting evidence highlights that EZH2 expression, activity and stability can be regulated by PTMs including phosphorylation, acetylation, ubiquitination, sumoylation and GlcNAcylation aside from its well-validated modifications in transcriptional and post-transcriptional levels. However, the precise regulatory mechanisms underlying EZH2 PTMs and whether other types of PTMs orchestrate in EZH2 remain largely unclear. In this review, we summarize current advances in the understanding of EZH2 regulation by PTMs and their associated biological functions during tumorigenesis.

Cell transfer therapy for cancer: past, present, and future.

Cell transfer therapy for cancer has made a rapid progress recently and the immunotherapy has been recognized as the fourth anticancer modality after operation, chemotherapy, and radiotherapy. Lymphocytes used for cell transfer therapy include dendritic cells, natural killer (NK) cells, and T lymphocytes such as tumor-infiltrating lymphocytes (TILs) and cytotoxic T lymphocytes (CTLs). In vitro activated or engineered immune cells can traffic to cancer tissues to elicit persistent antitumor immune response which is very important especially after immunosuppressive treatments such as chemotherapy. In this review, we overviewed recent advances in the exploration of dendritic cells, NK cells, and T cells for the treatment of human cancer cells.